CONTEXT: Graves' orbitopathy (GO) is probably caused by autoimmune reactions against autoantigen(s) shared by thyroid and orbital tissues sustained by intrathyroidal autoreactive T-lymphocytes infiltrating the orbit. Total thyroid ablation (TTA) may be beneficial for GO through removal of shared antigen(s) and autoreactive T-lymphocytes, but randomized studies are lacking. OBJECTIVE: Our objective was to evaluate the effects of TTA in patients with GO treated with iv glucocorticoids (GC). DESIGN/SETTING: A prospective, single-blind, randomized study was conducted at a referral center. PATIENTS/INTERVENTIONS: Sixty patients with mild to moderate GO were randomized into: 1) near-total thyroidectomy (TX); or 2) TX plus (131)I (TTA) groups, and then treated with iv GC. Patients were evaluated 3 and 9 months after iv GC. MAIN OUTCOME MEASURE: Overall improvement of GO at 9 months was the main outcome measure. RESULTS: The distribution of GO outcome at 9 months was significantly more favorable in TTA than in TX patients (P = 0.0014 by chi(2) test). A cumulative significant (P = 0.0054) difference between the two groups at 3 and 9 months was found using a generalized linear model. Radioiodine uptake test and thyroglobulin assay in a patient sample showed complete ablation in the majority of TTA, but not of TX patients. CONCLUSIONS: Compared with thyroidectomy alone, TTA is followed by a better outcome of GO in patients given iv GC. Whether TTA maintains this advantage in the long-term remains to be established.